Facilitating direct compaction tableting of fine cohesive APIs using dry coated fine excipients: Effect of the excipient size and amount of coated silica

The possibility of attaining direct compression (DC) tableting using silica coated fine particle sized excipients was examined for high drug loaded (DL) binary blends of APIs. Three APIs, very-cohesive micronized acetaminophen (mAPAP, 7 μm), cohesive acetaminophen (cAPAP, 23 μm), and easy-flowing ibuprofen (IBU, 53 μm), were selected. High DL (60 wt%) binary blends were prepared with different fine-milled MCC-based excipients (ranging 20- 37 μm) with or without A200 silica coating during milling. The blend flowability (flow function coefficient −FFC) and bulk density (BD) of the blends for all three APIs were significantly improved by 1 wt% A200 dry coated MCCs; reaching FFC of 4.28 from 2.14, 7.82 from 2.96, and > 10 from 5.57, for mAPAP, cAPAP, and IBU blends, respectively, compared to the uncoated MCC blends.

Highlights

60 wt% API (7–53 μm) binary blends with fine (20–37 μm) excipients investigated.

Flowability of 60 wt% fine API blends enhanced by milled and silica coated fine MCCs.

Positive impact of silica coating on tablet tensile strength (TS); >1.7 MPa achieved.

Less silica had a positive impact on TS, higher had a positive impact on flowability.

Adjusting the excipient size and silica amount enabled direct compression tableting.

No negative impact was observed on the tablet tensile strength (TS) by using dry coated MCCs despite lower surface energy of silica. Instead, the desired tablet TS levels were reached or exceeded, even above that for the blends with uncoated milled MCCs. The novelty here is that milled and silica coated fine MCCs could promote DC tableting for cAPAP and IBU blends at 60 wt% DL through adequate flowability and tensile strength, without having to dry coat the APIs. The effect of the silica amount was investigated, indicating lesser had a positive impact on TS, whereas the higher amount had a positive impact on flowability. Thus, the finer excipient size and silica amounts may be adjusted to potentially attain blend DC processability for high DL blends of fine APIs.

Materials

Microcrystalline Cellulose (MCC) Pharmacel 101 (MCC101), donated by DFE Pharma Corporation, USA, was used to prepare milled MCC powders, to be used as a filler. Aerosil A200 silica (A200), donated by Evonik Corporation, USA, was used to dry coat milled Pharmacel 101. Micronized Acetaminophen (mAPAP), coarse Acetaminophen (cAPAP), and Ibuprofen 50 (IBU) were selected as model drugs acquired or purchased from Mallinckrodt Pharmaceuticals (MO, USA), Changshu Huagang Pharmaceutical CO., Ltd.

Zhixing Lin, Bian Cabello, Christopher Kossor, Rajesh Davé, Facilitating direct compaction tableting of fine cohesive APIs using dry coated fine excipients: Effect of the excipient size and amount of coated silica, International Journal of Pharmaceutics, 2024, 124359, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124359.